Backgrounds
Acute peritonitis is a serious complication of abdominal surgeries. Left untreated, the inflammatory process is accompanied by disturbances in oxygen dynamics and may lead to septic reactions. We hypothesized that complement system activation and C5a generation is involved in the development of sepsis-induced cellular hypoxia. Therefore, we investigated the effects of C5a antagonist (C5aA) treatment on the alterations of peripheral microcirculation, oxygen consumption (VO2) and delivery (DO2) in a large animal model of intraabdominal sepsis.

Materials and Methods
Anesthetized minipigs were subjected to fecal peritonitis (0.7 g/kg autofaeces i.p.) without (n=7) or with C5aA treatment (4 mg/kg AcPepA, Nagoya, Japan, n=6) 19 hr after the insult. Invasive hemodynamic monitoring and blood gas analyses were started, VO2-DO2 values were calculated, and sublingual microcirculation parameters (the rate of perfused capillaries, by intravital orthogonal polarization spectral imaging technique) were recorded between the 16-24 hr of sepsis.

Results
In septic animals the DO2 (3680±310 ml/min/m2) and VO2 (510±85 ml/min/m2) values were elevated, while the oxygen extraction ratio (VO2-DO2 ratio <13%) was deteriorated significantly. These changes were accompanied by sublingual microcirculatory deficit, as compared with baseline. The C5aA treatment increased significantly the DO2 and VO2 values, the VO2-DO2 ratio (to 22%) and the perfusion rate of sublingual microcirculation.

Conclusion
These data demonstrate that inhibition of complement cascade components has beneficial effects on the oxygen extraction in experimental sepsis and suggest that the C5aA treatment could be a novel therapeutic opportunity to ameliorate the hypoxic consequences of septic inflammation.